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Influenza A H5N1 immigration is filtered out at some international borders.

Wallace RG, Fitch WM - PLoS ONE (2008)

Bottom Line: In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness.Pathogen dispersal, the functional relationships among disease ecologies across localities, and the efficacy of control efforts can also be inferred, all from viral genetic sequences alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, USA. rwallace@uci.edu

ABSTRACT

Background: Geographic spread of highly pathogenic influenza A H5N1, the bird flu strain, appears a necessary condition for accelerating the evolution of a related human-to-human infection. As H5N1 spreads the virus diversifies in response to the variety of socioecological environments encountered, increasing the chance a human infection emerges. Genetic phylogenies have for the most part provided only qualitative evidence that localities differ in H5N1 diversity. For the first time H5N1 variation is quantified across geographic space.

Methodology and principal findings: We constructed a statistical phylogeography of 481 H5N1 hemagglutinin genetic sequences from samples collected across 28 Eurasian and African localities through 2006. The MigraPhyla protocol showed southern China was a source of multiple H5N1 strains. Nested clade analysis indicated H5N1 was widely dispersed across southern China by both limited dispersal and long distance colonization. The UniFrac metric, a measure of shared phylogenetic history, grouped H5N1 from Indonesia, Japan, Thailand and Vietnam with those from southeastern Chinese provinces engaged in intensive international trade. Finally, H5N1's accumulative phylogenetic diversity was greatest in southern China and declined beyond. The gradient was interrupted by areas of greater and lesser phylogenetic dispersion, indicating H5N1 migration was restricted at some geopolitical borders. Thailand and Vietnam, just south of China, showed significant phylogenetic clustering, suggesting newly invasive H5N1 strains have been repeatedly filtered out at their northern borders even as both countries suffered recurring outbreaks of endemic strains. In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.

Conclusions: The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness. Pathogen dispersal, the functional relationships among disease ecologies across localities, and the efficacy of control efforts can also be inferred, all from viral genetic sequences alone.

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Related in: MedlinePlus

Generalized Mantel Test Across H5N1 Distance Matrices.Pairwise Mantel test for correspondence based on Spearman correlation ranks for six distance matrices defined for H5N1 phylogeny of 481 hemagglutinin nucleotide sequences across 28 Eurasian and African localities: 1) migration events through the phylogeny symmetricized across the migration matrix diagonal (SME), 2) differences in isolates sample size (SS), 3) geographic distances (Geo), 4) UniFrac distances, 5) mean phylogenetic distances (MPD), and 6) mean nearest neighbor distances (MNND). Correlations are blocked out in color and upper-tail P values in gray scale. P values for pairwise comparisons between localities significant under false discovery rate correction are boxed in gold borders.
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pone-0001697-g005: Generalized Mantel Test Across H5N1 Distance Matrices.Pairwise Mantel test for correspondence based on Spearman correlation ranks for six distance matrices defined for H5N1 phylogeny of 481 hemagglutinin nucleotide sequences across 28 Eurasian and African localities: 1) migration events through the phylogeny symmetricized across the migration matrix diagonal (SME), 2) differences in isolates sample size (SS), 3) geographic distances (Geo), 4) UniFrac distances, 5) mean phylogenetic distances (MPD), and 6) mean nearest neighbor distances (MNND). Correlations are blocked out in color and upper-tail P values in gray scale. P values for pairwise comparisons between localities significant under false discovery rate correction are boxed in gold borders.

Mentions: The test for global convergence across distance matrices (CADM) rejected overall incongruence (P = .0001)—at least two of the matrices converged (Table S2). The a posteriori convergence tests we next conducted failed to reject the hypothesis that the matrix of symmetricized migration events (P = .30) was incongruent with the other five matrices. The generalized Mantel test, based on Spearman correlation of ranks and a false discovery rate correction, identified seven pairwise comparisons as significantly convergent (Figure 5). In rank order of the strength of correlation, the significant pairs were MPD-UniFrac (r = .93), MPD-MNND (.78), MNND-UniFrac (.74), geographic distance-MNND (.29), geographic distance-MPD (.27), geographic distance-UniFrac (.23), and sample size difference-MNND (.22).


Influenza A H5N1 immigration is filtered out at some international borders.

Wallace RG, Fitch WM - PLoS ONE (2008)

Generalized Mantel Test Across H5N1 Distance Matrices.Pairwise Mantel test for correspondence based on Spearman correlation ranks for six distance matrices defined for H5N1 phylogeny of 481 hemagglutinin nucleotide sequences across 28 Eurasian and African localities: 1) migration events through the phylogeny symmetricized across the migration matrix diagonal (SME), 2) differences in isolates sample size (SS), 3) geographic distances (Geo), 4) UniFrac distances, 5) mean phylogenetic distances (MPD), and 6) mean nearest neighbor distances (MNND). Correlations are blocked out in color and upper-tail P values in gray scale. P values for pairwise comparisons between localities significant under false discovery rate correction are boxed in gold borders.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2244808&req=5

pone-0001697-g005: Generalized Mantel Test Across H5N1 Distance Matrices.Pairwise Mantel test for correspondence based on Spearman correlation ranks for six distance matrices defined for H5N1 phylogeny of 481 hemagglutinin nucleotide sequences across 28 Eurasian and African localities: 1) migration events through the phylogeny symmetricized across the migration matrix diagonal (SME), 2) differences in isolates sample size (SS), 3) geographic distances (Geo), 4) UniFrac distances, 5) mean phylogenetic distances (MPD), and 6) mean nearest neighbor distances (MNND). Correlations are blocked out in color and upper-tail P values in gray scale. P values for pairwise comparisons between localities significant under false discovery rate correction are boxed in gold borders.
Mentions: The test for global convergence across distance matrices (CADM) rejected overall incongruence (P = .0001)—at least two of the matrices converged (Table S2). The a posteriori convergence tests we next conducted failed to reject the hypothesis that the matrix of symmetricized migration events (P = .30) was incongruent with the other five matrices. The generalized Mantel test, based on Spearman correlation of ranks and a false discovery rate correction, identified seven pairwise comparisons as significantly convergent (Figure 5). In rank order of the strength of correlation, the significant pairs were MPD-UniFrac (r = .93), MPD-MNND (.78), MNND-UniFrac (.74), geographic distance-MNND (.29), geographic distance-MPD (.27), geographic distance-UniFrac (.23), and sample size difference-MNND (.22).

Bottom Line: In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness.Pathogen dispersal, the functional relationships among disease ecologies across localities, and the efficacy of control efforts can also be inferred, all from viral genetic sequences alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, USA. rwallace@uci.edu

ABSTRACT

Background: Geographic spread of highly pathogenic influenza A H5N1, the bird flu strain, appears a necessary condition for accelerating the evolution of a related human-to-human infection. As H5N1 spreads the virus diversifies in response to the variety of socioecological environments encountered, increasing the chance a human infection emerges. Genetic phylogenies have for the most part provided only qualitative evidence that localities differ in H5N1 diversity. For the first time H5N1 variation is quantified across geographic space.

Methodology and principal findings: We constructed a statistical phylogeography of 481 H5N1 hemagglutinin genetic sequences from samples collected across 28 Eurasian and African localities through 2006. The MigraPhyla protocol showed southern China was a source of multiple H5N1 strains. Nested clade analysis indicated H5N1 was widely dispersed across southern China by both limited dispersal and long distance colonization. The UniFrac metric, a measure of shared phylogenetic history, grouped H5N1 from Indonesia, Japan, Thailand and Vietnam with those from southeastern Chinese provinces engaged in intensive international trade. Finally, H5N1's accumulative phylogenetic diversity was greatest in southern China and declined beyond. The gradient was interrupted by areas of greater and lesser phylogenetic dispersion, indicating H5N1 migration was restricted at some geopolitical borders. Thailand and Vietnam, just south of China, showed significant phylogenetic clustering, suggesting newly invasive H5N1 strains have been repeatedly filtered out at their northern borders even as both countries suffered recurring outbreaks of endemic strains. In contrast, Japan, while successful in controlling outbreaks, has been subjected to multiple introductions of the virus.

Conclusions: The analysis demonstrates phylogenies can provide local health officials with more than hypotheses about relatedness. Pathogen dispersal, the functional relationships among disease ecologies across localities, and the efficacy of control efforts can also be inferred, all from viral genetic sequences alone.

Show MeSH
Related in: MedlinePlus